Assessment of Different Circulating Tumor Cell Platforms for Uveal Melanoma: Potential Impact for Future Routine Clinical Practice

Abstract

Liquid biopsy and circulating tumor cell (CTC) screening has gained interest over the last two decades for detecting almost all solid malignancies. To date, the major limitation in terms of the applicability of CTC screening in daily clinical practice is the lack of reproducibility due to the high number of platforms available that use various technologies (e.g., label-dependent versus label-free detection). Only a few studies have compared different CTC platforms. The aim of this study was to compare the efficiency of four commercially available CTC platforms (Vortex (VTX-1), ClearCell FX, ISET, and Cellsearch) for the detection and identification of uveal melanoma cells (OMM 2.3 cell line). Tumor cells were seeded in RPMI medium and venous blood from healthy donors, and then processed similarly using these four platforms. Melan-A immunochemistry was performed to identify tumor cells, except when the Cellsearch device was used (automated identification). The mean overall recovery rates (with mean recovered cells) were 39.2% (19.92), 22.2% (11.31), 8.9% (4.85), and 1.1% (0.20) for the ISET, Vortex (VTX-1), ClearCell FX, and CellSearch platforms, respectively. Although paramount, the recovery rate is not sufficient to assess a CTC platform. Other parameters, such as the purpose for using a platform (diagnosis, genetics, drug sensitivity, or patient-derived xenograft models), reproducibility, purity, user-friendliness, cost-effectiveness, and ergonomics, should also be considered before they can be used in daily clinical practice and are discussed in this article.

Recent Advances in Molecular and Genetic Research on Uveal Melanoma

“…Even now, the existence of numerous platforms using various technologies to detect the tumor cells (e.g., label-dependent or label-free detection) impact the reproducibility and applicability of CTC screening in daily clinical practice. A recent study comparing four platforms to capture UM cells in blood or culture medium, including the immunomagnetic CellSearch platform that was approved by the FDA in the early 2000s for the diagnosis and prognosis of metastatic cancers, failed to recover enough UM cells for further comparisons or molecular analyses [ 95 ]. Capturing and counting CTCs have traditionally been difficult because methods often target just a single surface antigen.…”

Circulating Tumor Cells as Predictive and Prognostic Biomarkers in Solid Tumors

“…Unlike regular blood cells, CTCs are characterized by the presence of epithelial markers, such as epithelial cell adhesion molecules (EpCAM) and cytokeratin (CK) [38,39]. Specific techniques that leverage this principle include the conjugation of antibodies to magnetic nanoparticles and the use of microfluidics [40,41]. While there is some variability in the phenotypic and functional definitions of CTCs across different studies, it is widely agreed upon that CTCs typically lack the CD45 marker and exhibit the presence of EpCAM and CK [42].…”